Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100
Murielle M. Véniant, … , Rosemary L. Walzem, Stephen G. Young
Murielle M. Véniant, … , Rosemary L. Walzem, Stephen G. Young
Published December 15, 2000
Citation Information: J Clin Invest. 2000;106(12):1501-1510. https://doi.org/10.1172/JCI10695.
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Article

Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100

Abstract

Apo-E–deficient apo-B100–only mice (Apoe–/–Apob100/100) and LDL receptor–deficient apo-B100–only mice (Ldlr–/–Apob100/100) have similar total plasma cholesterol levels, but nearly all of the plasma cholesterol in the former animals is packaged in VLDL particles, whereas, in the latter, plasma cholesterol is found in smaller LDL particles. We compared the apo-B100–containing lipoprotein populations in these mice to determine their relation to susceptibility to atherosclerosis. The median size of the apo-B100–containing lipoprotein particles in Apoe–/–Apob100/100 plasma was 53.4 nm versus only 22.1 nm in Ldlr–/–Apob100/100 plasma. The plasma levels of apo-B100 were three- to fourfold higher in Ldlr–/–Apob100/100 mice than in Apoe–/–Apob100/100 mice. After 40 weeks on a chow diet, the Ldlr–/–Apob100/100 mice had more extensive atherosclerotic lesions than Apoe–/–Apob100/100 mice. The aortic DNA synthesis rate and the aortic free and esterified cholesterol contents were also higher in the Ldlr–/–Apob100/100 mice. These findings challenge the notion that all non-HDL lipoproteins are equally atherogenic and suggest that at a given cholesterol level, large numbers of small apo-B100–containing lipoproteins are more atherogenic than lower numbers of large apo-B100–containing lipoproteins.

Authors

Murielle M. Véniant, Meghan A. Sullivan, Sun K. Kim, Patricia Ambroziak, Alice Chu, Martha D. Wilson, Marc K. Hellerstein, Lawrence L. Rudel, Rosemary L. Walzem, Stephen G. Young

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Figure 2

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Lipoprotein sizes in the four different groups of mice. The median diame...
Lipoprotein sizes in the four different groups of mice. The median diameter of lipoproteins in Apoe–/–Apob100/100 mice (n = 15) was 140% larger than in Ldlr–/–Apob100/100 (n = 21) mice, 90% larger than in Ldlr–/–Apob+/+ mice (n = 17), and 50% larger than in Apoe–/–Apob+/+ mice (n = 16). The size of VLDL (d < 1.006 g/ml) particles ranged from an average of 33.4 nm in Ldlr–/–Apob100/100 mice to 61 nm in Apoe–/–Apob100/100 mice; the size of IDL (d = 1.006–1.020 g/ml) particles ranged from an average of 27 nm in Ldlr–/–Apob100/100 mice to 38 nm in Apoe–/–Apob100/100 mice; the size of LDL (d = 1.020–1.052 g/ml) particles was 23 nm in Apoe–/–Apob100/100 plasma, 20 nm in Apoe–/–Apob+/+ plasma, 22 nm in Ldlr–/–Apob100/100 plasma, and 19 nm in Ldlr–/–Apob+/+ plasma. The difference in size between the bottom and top deciles of particles was 64.0 nm for Apoe–/–Apob100/100 mice, 27.2 nm for Apoe–/–Apob+/+ mice, 17.8 nm for Ldlr–/–Apob+/+ mice, and 17.0 nm for Ldlr–/–Apob100/100 mice.